British Medical Bulletin (1978) Vol. 34, No. 2, pp. 163-167

DIAGNOSIS OF DEEP-VEIN THROMBOSIS N Browse thennography, thefibrinogenuptake test, x-ray phlebography and isotope phlebography. 1 Clinical Examination

DIAGNOSIS OF DEEP-VEIN THROMBOSIS

The symptoms and signs of deep-vein thrombosis fall into two groups, those caused by venous obstruction and those caused by the "inflammatory" changes around the thrombus. Venous obstruction causes swelling of the leg, dilatation of the superficial veins, an increase in skin temperature and, in severe cases, a bluish discoloration of the skin of the leg. The inflammatory response in the vein wall causes pain and tenderness. Signs such as swelling, discoloration and tenderness are easy to detect by simple inspection and palpation and many clinicians consider that routine daily inspection of the lower limbs of post-operative patients for such signs is an essential part of management. Accuracy. When the physical signs of venous obstruction are present, such as swelling around the ankle or venous distension, one has an 80% chance of making a correct diagnosis of deep-vein thrombosis (McLachlin et al. 1962). Regrettably, the common symptoms, pain and tenderness, are extremely unreliable. Only 50% of those patients who complain of calf tenderness after an operation have a deepvein thrombosis. In the other half the tenderness is secondary to other causes such as muscle strain, cramps, disuse and pressure from resting in bed. Thus the text-book physical signs of deep-vein thrombosis are by no means a certain indication of the presence of thrombosis (Lambie et al. 1970; Cranley et al. 1976). Indeed, the most important fact to remember is that two-thirds of the patients with thrombosis have no physical signs. This means that clinical examination cannot be used as a screening technique to detect all thromboses. But clinical examination is easy and harmless and the detection of physical signs does alert the clinician to the possible danger of thrombosis, although it might be more logical just to remember that between one-third and one-half of all the patients in medical and surgical wards have deep-vein thrombosis, and act accordingly.

NORMAN BROWSE MD FRCS Department of Surgery St Thomas's Hospital Medical School, London

1 2 3 4 5 6 7 8

Clinical examination The Doppler flow detector Impedance plethysmography Thennography Fibrinogen uptake test Isotope venography Phlebography Discussion References

Since the time that Rudolf Virchow first described the connection between peripheral vein thrombosis and pulmonary thrombo-embolism the morbid anatomists have repeatedly told the physicians that venous thrombosis is a common complication of all forms of surgical, medical and obstetric disease. As recently as 1961, Sevitt & Gallagher demonstrated that 80% of patients who died seven days after a fracture of the neck of the femur had deep-vein thrombosis; yet in spite of such studies clinicians did not accept the ubiquity of venous thrombosis in clinical practice until the development of the fibrinogen uptake test, which revealed the presence of calf-vein thrombosis in as many as 50% of the patients undergoing some forms of major surgery. Venous thrombosis presents two clinical problems. The first is that any thrombus might fragment and become a pulmonary embolus and, if it is large enough, cause the patient's death. The second is that the thrombus will damage the valves in the peripheral veins and so disorganize the muscle pump, ultimately causing varicose veins and the post-phlebitic syndrome. To avoid such complications, the clinician must either prevent all forms of thrombosis, or diagnose the thrombosis in its early stages so that it can be treated. For these purposes he needs two different types of diagnostic aid. For research into methods of prophylaxis he needs screening techniques that detect all thrombi as soon as they appear. For decisions concerning the treatment of established thrombosis he needs techniques that provide the maximum information about the presence, extent and nature of the thrombus. This paper will concentrate on the advantages, disadvantages and applications of the methods of investigation that are currently available, without describing the techniques in detail, because they have been described frequently in marry journals. The accuracy, risks and disadvantages, special advantages, and clinical applicability of each test, including a comment on the suitability of the test as a method of screening for research or clinical diagnosis, will be discussed. The following methods of investigation will be described: clinical examination, ultrasound, impedance plethysmography,

2 The Doppler Flow Detector Large thrombi in major veins are likely to obstruct venous blood flow. The Doppler ultrasound flow detector is an instrument that can detect changes in the rate of venous or arterial blood flow. The technique is simple. A transducer, which contains an ultrasound transmitter and receiver, is placed over a large vein. The tissues upstream to the vein are squeezed to produce a sudden increase in the rate of blood flow in the vein under the transducer. This change in flow velocity causes a change in the frequency of the ultrasound waves being reflected from the red corpuscles (the Doppler effect), which is electronically amplified into an audible noise. Thus if the transducer is placed over the femoral vein just below the groin and the calf squeezed, a swishing sound is heard corresponding to the sudden increase of femoral vein blood flow. This implies that the veins between the squeezing hand and the transducer are patent (Strandness et al. 1967; Sigel et al. 1968; Evans & Cockett, 1969). Accuracy. The published studies of the accuracy of this technique show that it is approximately 80% correct in detecting thrombi in the large veins above the calf. The 163

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DIAGNOSIS OF DEEP-VEIN THROMBOSIS N Browse 15-20% false-negative results are associated with early nonadherent thrombi not large enough to produce a significant obstruction to the flow of blood in the vein. Unfortunately these are usually the young fresh thrombi, which are made of a soft fragile red thrombus and often become pulmonary emboli. The failure of this method to detect this type of thrombus is a serious deficiency. Another cause of a false-negative result is the presence of a large collateral vein by-passing the obstructed vein and carrying sufficient blood to change the rate of flow above the block when the tissues upstream to the vein are squeezed, so producing the swishing sound and suggesting that the vein is patent. Risks and disadvantages. I have been told of two cases of pulmonary embolism occurring immediately after squeezing the calf muscles. It is tempting to think that the squeezing caused the embolus, but many thousands of Doppler ultrasound investigations have been performed on patients with calf-vein thrombosis and, with the exception of these two case reports, there is no reason to think that gently squeezing the calf does any harm to the calf or causes pulmonary embolism. The principal disadvantage of the method is that it cannot detect small thrombi within the calf muscles and is less accurate when applied to the vena cava or iliac veins, even when a low-frequency 2 MHz transmitter that is able to penetrate through the abdominal wall to the vena cava is used, because the reflections caused by gas in the bowel distort the reflections from the vessels. Special advantages. Ultrasound's main advantage is its simplicity. The apparatus is relatively cheap and the major veins of the lower limb can be checked in one or two minutes. Clinical applicability. In spite of the anatomical limitations and the 80 % accuracy, this method is of considerable clinical value in those situations where the clinician has reason to suspect the presence of a thrombus, e.g. when the patient has the physical signs of a pulmonary embolus or has a swollen leg, for it enables the clinician to check the patency of the major deep veins as part of his clinical examination (Yao et al. 1972; Meadway et al. 1975). If they appear to be patent, he can be reasonably certain that there is not a large thrombus in the iliofemoral venous segment waiting to become an embolus. On the other hand, if the test shows an occluded vein he must proceed urgently to phlebography to define the state and extent of the thrombus. Screening. It has been suggested that the Doppler ultrasound technique could be used daily on all in-patients to detect any thrombus as soon as it appears in the popliteal or femoral vein. One small study of this suggestion (McDroy, 1972) detected 16 occluded veins in 322 legs, and Evans (1970) detected four occluded veins in 1717 examinations of patients, when examining patients twice a week. Thus the yield of the method when used as a screening technique is small and probably does not justify the time and expense. Neither of these studies was able to detect the number of false-negative results, because they were not controlled with phlebography. A thrombus can grow extremely quickly and any screening technique that is used on consecutive or alternate days might well miss a thrombus that had grown up the femoral vein and become an embolus in the 24 hours between examinations. Although this limitation applies to all forms of screening it is particularly significant with this method, because ultrasound is unable to detect a thrombus until it has reached a size large enough to obstruct a major vein.

3 Impedance Plethysmography All forms of plethysmography are based on a measurement of tissue volume. The impedance plethysmograph uses an electrical technique to measure calf circumference. The object of measuring the volume of the calf is to examine the changes in calf volume produced by venous congestion, and the rate of emptying of the calf after releasing the congestion. If a thrombus is obstructing theflowof blood from the veins of the limb, the rate of venous emptying, after being distended by proximal venous occlusion, will be prolonged. In other words plethysmographic techniques are just another way of detecting an obstruction in the large veins draining the limb. The apparatus is simple, but more expensive than the Doppler ultrasound apparatus, is not invasive and does not cause pain. The strain gauges that detect the changes in tissue volume are placed around the calf, an inflatable cuff (which requires a reservoir of gas) is placed above the knee, and an electrical recorder produces a tracing of the changes in calf volume during and after venous occlusion. Each examination takes 10-15 minutes (Wheeler et al. 1971; Hull et al. 1976). Accuracy. Just as with the ultrasound technique, this method cannot detect thrombi that do not produce a ygnrfiremt obstruction to venous blood flow. Thus it is less than 50% accurate in detecting calf-vein thrombosis, but 80-90% accurate with major femoral and iliac vein thromboses, an over-all false-negative rate of 25-35 %. False-positive results are uncommon. It has been claimed that the patterns of volume change are not reproducible from day to day. Risks and disadvantages. There are no apparent risks associated with this technique. The inflatable cuff is unlikely to fragment a thrombus and cause an embolus and is not uncomfortable for the patient Advantages. The special advantages of the technique are its ease of application and its potential for day-to-day follow-up studies. Clinical applicability. Although the technique is not completely accurate it can be used, in the same way as Doppler ultrasound, to screen patients suspected on clinical grounds of having a thrombus into those with definite venous obstruction and those without, provided that the operator always remembers the deficiencies of the method. Management after the initial study with impedance plethysmography follows the same plan as that described for the ultrasound technique. Because this test cannot detect an early calf-vein thrombus it is of no value as a screening test for detecting all early thrombi in all patients (Bergquist et al. 1973; Hume etal.1916). The above comments on impedance plethysmography apply to other methods of plethysmography (Cranley et al. 1975). 4 Thermography It has often been observed that legs containing thrombosed veins, particularly a thrombus that is obstructing the venous outflow of the limb, are warmer than normal (Provan, 1965). This abnormality can be detected by the hand, or more accurately with an infrared camera. The legs of the patient must be exposed to allow equilibration of skin and room temperature, and elevated to empty the superficial veins. The heat radiating from the legs is reflected on to an infrared camera by means of a heat-reflecting mirror placed at an angle of 45° over the legs. The infrared camera 164 Br. Med. Bull. 1978

DIAGNOSIS OF DEEP-VEIN THROMBOSIS

the background count from the soft tissues, large blood-vessels and the bladder masks the relatively small increases in activity that occur in thrombi. Below the middle of the thigh the method is 95% accurate, when compared with phlebography and autopsy (Morris & Mitchell, 1977). False-positive readings occur whenever there is inflammation, haematoma or marked oedema. Thus local trauma, arthritis and generalized oedema of the leg should be excluded before using the test. If this is done the number of false-negative results is very small. In fact many think that the test is more accurate in the calf than phlebography, and that small accumulations of radioactivity associated with negative phlebograms are thrombi that are too small or too far from the main veins to be detected by phlebography. The main cause of false-negative readings is a thrombus that is more than five days old. A thrombus younger than this can be expected to take up some labelled fibrinogen, but once a thrombus isfivedays old the test is only 50 % accurate (Browse et al. 1971). Another, but nowadays unusual, cause of a false-negative result is poor labelling of thefibrinogenso that the iodine and the fibrinogen dissociate soon after injection. Risks and disadvantages. The radiation dose to each patient is small and safe. The transmission of viral hepatitis is a theoretical hazard because fibrinogen cannot be sterilized by autoclaving, but many thousands of doses of labelled fibrinogen nave been used in the United Kingdom since 1968 and there have been no outbreaks of hepatitis. This reflects the caution and responsible attitude of the makers of the fibrinogen who have used as their source of fibrinogen a small pool of donors who are hepatitis B surface antigen negative and who are known to have been free of jaundice and any liver disease for the 2\ years preceding the donation of the blood. Although the risk of hepatitis is negligible, some research workers still prefer to make their own fibrinogen from one or two carefully screened donors. The major disadvantage of the fibrinogen uptake test is that it is applicable only to the lower thigh and calf. A thrombus in the upper half of the thigh, which may be large and become a lethal pulmonary embolus, is often undetected. The method is costly in equipment, use of isotopes and the technician's time. Each examination takes 15-20 minutes and cannot be performed until 24 hours after the injection of the isotope, making the test useless in an urgent clinical situation. This deficiency is partly counterbalanced by the ability to repeat the examination as often as necessary, without discomfort to the patient or until the radioactivity has decayed below an acceptable level. Even then further examinations can be performed if the patient is given a further dose of the labelled fibrinogen. The technique is not so accurate when used for the diagnosis of established thrombosis and fails once the thrombus begins to age and retract (Browse et al. 1971). Clinical applicability. Thefibrinogenuptake test is extremely valuable as a research tool because it is probably the most accurate method of detecting fresh small thrombi in the calf, and by revealing a high incidence of post-operative thrombosis permits clinical trials to be kept to a reasonable size. As a clinical toolit has a limited place. It is rarely used for the diagnosis of established thrombosis because phlebography is more accurate and provides more information; but it is useful for the investigation of the patient who presents with pain in the calf, in whom ultrasound or plethysmography has shown

produces a Polaroid photograph of skin temperature in which the warm areas are lighter in colour than the cold areas— which are blade. A deep-vein thrombus in the calf makes the whole of the lower leg warmer, including the skin covering the subcutaneous surface of the tibia and patella. The technique can be used at the bedside and an examination takes 10-20 minutes (Cooke & Pflcher, 1974). Accuracy. The studies that have compared thermography with phlebography claim a 90 % accuracy for the diagnosis of calf-vein and femoral vein thrombosis (Cooke & Pilcher, 1974; Bergqvist et al. 1975). The technique cannot detect thrombi in the iliac veins or vena cava which are not obstructing venous blood flow, and other causes of inflammation such as arthritis, superficial thrombophlebitis and cellulitis will give falsepositive readings; but these conditions should be detectable on clinical examination. Special advantages. The technique is totally non-invasive and can be repeated as often as the investigator wishes. Clinical applicability. This method has not been widely adopted for clinical use but some workers have used it for research purposes because it is reasonably accurate and can be repeated as often as required. The apparatus is very expensive and many clinicians feel that this factor outweighs the technique's clinical value.

5 Flbrinogen Uptake Test The fibrinogen uptake test came into clinical use in 1968 and has since been used extensively and discussed thoroughly in many papers (e.g. Flanc et al. 1968; Negus et al. 1968). The success of the technique depends upon the incorporation of circulating radioactive fibrinogen into a forming or recently formed thrombus, so concentrating the radioactivity to a degree that makes it detectable by external scintillation counting. The important points of the technique are as follows: the thyroid gland must be saturated with iodine before giving the labelledfibrinogen,by giving oral potassium iodide, to stop it taking up any radioactive iodine. Higher count rates are obtained over the thrombus if the labelled fibrinogen is given before the thrombus forms. This means that the method is most useful for surgical patients when the labelled fibrinogen may be given before, or immediately after, the operation. The legs can be examined with a scintillation counter connected to either a ratemeter or a sealer and timer. Whichever technique is used, the results are expressed as a percentage of the precordial count. The diagnostic criteria vary slightly according to the method used (Roberts, 1975). If a small (2 inch1) collimator is used a difference of 20 between the count rate of adjacent points on the same limb, or between similar points on both limbs, indicates a thrombus. If a wide (4 inch) collimator is used a difference of 15 between adjacent count rates indicates a thrombus. Once the labelled fibrinogen has been given, and 24 hours have elapsed for its incorporation into the thrombus, the leg may be examined as often as required provided that there is sufficient radioactivity in the thrombus to give significant count rates when compared with the background activity. Accuracy. The method can be used to examine the legs only below the middle of the thigh, because above this level U inch - 25.4 mm.—ED.

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DIAGNOSIS OF DEEP-VEIN THROMBOSIS the main veins to be patent, and where speed of diagnosis is not essential. In these patients it can also be used to follow the natural history of the thrombus. Screening. Although the fibrinogen uptake test has become an important screening tool for research it has not been adopted as a method of screening all patients, because of its cost and the fact that it rarely reveals thrombi of clinical significance. To use it on all patients in order to detect the 5-10% of thrombi that propagate from the calf into the popliteal vein, whilst ignoring those that start in the thigh and pelvis, cannot be justified. 6 Isotope Venography If a radioactive isotope is injected into a peripheral vein below a major vein occlusion and the legs are scanned with a Y camera immediately after the injection, it is possible to detect the isotope trapped below the blocked vein (Webber et at. 1969; Rosenthall & Greyson, 1970; Duffy et al. 1973; Webber et al. 1974). Furthermore, some of the isotope will adhere to the surface of a thrombus and this can also be detected. This technique is known as isotope venography and has been developed because it is a convenient way of combining a screening examination of the legs with a conventional lung scan. The technique is simple but the apparatus complex. The labelled particles (labelled albumin aggregates) are readily available, but the apparatus can be used only in the isotope department. Polaroid photographs of the y-camera scans of both lower limbs are taken one or two minutes after injecting the isotope. " H o t " areas are seen below obstructed veins and in areas of inflammation. The conventional lung scan is then performed. Accuracy. Very few studies have compared the accuracy of this method with that of phlebography. Those that have been performed suggest an 80 % accuracy rate, but the method does not give an accurate indication of the site of the thrombus. False-negative results are common with small thrombi that do not obstruct venous blood flow. False-positive results occur when there are areas of inflammation or oedema. Risks and disadvantages. The radiation hazard is negligible. The main disadvantages are that the patient must be examined by the y camera in the isotope department and that y cameras are very expensive. These reasons make it unlikely that this technique will become a routine method of diagnosis, but it is very useful for clinical research studies that require to know the incidence of peripheral thrombosis and pulmonary embolism. Special advantages. The ability to screen the limbs and get a lung scan from a single intravenous injection has obvious advantages. 7 Phlebography Phlebography is the standard technique used for the diagnosis of deep-vein thrombosis and is the method against which all others are compared. Many variations of technique have been described but the basis of them all is the intravenous injection of a radio-opaque contrast medium into a foot vein below a tourniquet placed around the ankle, which forces the contrast medium into the deep veins. Calf-vein opacification can be increased by the application of a tourniquet above the knee. At a later stage, when this tourniquet is released, the flood of contrast medium

N Browse

into the veins of the thigh and pelvis gives better opacification of these veins. This technique is known as bipedal ascending phlebography and can be used on 95 % of patients with deepvein thrombosis (Bauer, 1940; DeWeese & Rogoff, 1959; Thomas, 1972). On a few occasions the foot and ankle are so swollen that the radiologist cannot find a vein for an intravenous injection. In these circumstances the veins can be opacified via an intra-osseous injection into the os calcis, the tibia, the femur or the greater trochanter. Alternatively the femoral and the iliac veins can be displayed by a direct femoral vein injection (Thomas et al. 1970). The quality of phlebograms has been improved over the last 20 years by the development of better, less toxic contrast materials and the use of the image intensifier which enables the radiologist to see that the veins arefilledwith contrast medium before taking the films. A series offilmstaken blindly without knowing where the dye has gone is often inadequate. The diagnostic criteria of thrombosis are the presence of a filling defect in the contrast medium on more than one film or, if a vein is completely occluded, the presence of dye above and below an occluded segment and in the veins around it (DeWeese & Rogoff, 1963; Thomas et al. 1971). Accuracy. Although phlebography is used as the yardstick against which other methods are compared it is not itself completely accurate, but for obvious reasons there are no studies which have compared diagnosis by phlebography during life with the diagnosis of thrombosis by autopsy. It is obviously impossible to opacify every vein. The veins least well filled by ascending phlebography are the muscle veins of the calf, the tributaries of the profunda vein in the thigh, and the tributaries of the internal iliac vein in the pelvis. In spite of these deficiencies phlebography probably detects at least 95 % of peripheral thrombi. False-positive interpretations occur when inadequate mixing of the blood and contrast medium gives an appearance similar to a filling defect. Careful inspection of the radiographs usually shows that such appearances vary from film to film—a feature inconsistent with the diagnosis of thrombosis. Streaming of the contrast medium has a typical linear streaky appearance and is easily recognized. Blood entering an opacified vein often causes a spherical or oval defect (a "knothole"), and this common cause of false-positive reports is recognized by its shape and situation. The entry of the profunda femoris vein often causes a knot-hole in an otherwise opacified femoral vein, which gets mistakenly diagnosed as a small thrombus. Non-filling is also a common cause of false-positive reports and is usually a technical fault. Nonfilling caused by thrombosis is easy to recognize because it is always associated with collateral veins. False-negative results are caused by the limitations of the technique already discussed and by technical failures. Risks and disadvantages. The main disadvantage of phlebography is the requirement to take the patient to the ;e-ray department and the cost of modern x-ray equipment and of the radiologist's time. Injections into foot veins are uncomfortable and distention of the leg veins by the contrast medium is sometimes painful, but in my experience most patients are prepared to have the investigation repeated; so pain cannot be classed as a serious disadvantage. Minor degrees of superficial thrombophlebitis at the site of the injection are common. Very rarely (0.1%), extensive extravasation of the contrast medium or retrograde flow into the small venules of the foot damage the skin of the toes or the

166 Br. Med. Bull. 1978

DIAGNOSIS OF DEEP-VEIN THROMBOSIS N Browse purposes, either to screen all patients or to confirm his clinical diagnosis and obtain information for management. The descriptions above reveal that the methods most suitable for screening are the fibrinogen uptake test, the Doppler ultrasound flow detector and impedance plethysmography. None of these techniques is completely accurate, except perhaps the fibrinogen uptake test in the calf, but they cause the patient no discomfort and can be repeated as often as required. The high degree of accuracy of the fibrinogen uptake test below the knee makes it the method of choice for most research projects, but if the upper femoral and iliac veins are to be screened the researcher must use one of the other two techniques as well, or, better still—phlebography. Phlebography is the only acceptable method for the diagnosis of existing thrombosis. The other methods are too inaccurate and do not give the type of information that the clinician requires for management. Phlebography is essential if the patient has had a pulmonary embolus or has the signs of massive leg thrombosis, but it cannot be performed on every patient suspected of having a minor deep-vein thrombus on the basis of unreliable physical signs such as calf tenderness. In these circumstances most clinicians prefer to use one of the simple tests of major vein patency, such as the Doppler flow detector or impedance plethysmography, and proceed to phlebography only if the tests show a major vein abnormality. If they show that the major veins are patent then the diagnosis can be confirmed or denied at leisure with the fibrinogen uptake test, and watched with the same technique from day to day, so that treatment can be begun if the thrombus shows signs of extending. Treatment with anticoagulants, thrombolytic agents or surgery should never be given without an objective positive diagnosis.

sole of the foot and may cause superficial gangrene (Thomas, 1970). Many clinicians think that the injection of contrast medium into thrombosed veins will exacerbate the thrombosis. This does not occur provided that the radiologist insures that the patient exercises the legs vigorously to clear the deep veins of contrast medium, and checks with the image intensifier that this has occurred. Value. Phlebography reveals not only the presence of a thrombus but its extent and its nature. A young thrombus has a smooth edge, a " ground-glass " surface and does not usually adhere to the vein wall. As it ages it adheres to the vein wall, becomes a more-defined filling defect and develops an irregular edge which is outlined by a dark edge of contrast medium. These features enable the radiologist to estimate the age to within 7-10 days and to decide whether the thrombus is firmly fixed in the vein. This information is not available from any other technique and is extremely helpful when deciding clinical management. Phlebography is therefore the basic clinical tool for diagnosis and management decisions and for these purposes is far superior to any other method of diagnosis. Screening. Phlebography is unsuitable for screening all patients because it is time consuming, has to be done in the x-ray department, is uncomfortable and is not easily repeatable. It is used for research purposes only when it is essential to study the femoral and iliac veins. 8 Discussion The introduction to this paper stated that the clinician needs methods for detecting deep-vein thrombosis for two

Bauer G (1940) Acta Chir. Scand. suppl. no. 61, p. 33 Bergquist E, Bcrgqvist D, Bronge A, Dahlgren S & Hallbook T (1973) Uppsala J. Med. Sd. 78.191-199 Bergqvist D, Dahlgren S, Efeing 6 & Hallb&ok T (1975) Br. Med. J. 4,684-685 Browse N L, Clapham W F, Croft D N, Jones D J, Thomas M L & Williams J O (1971) Br. Med. J. 4, 325-328 Cooke E D & Pilcber M F (1974) Br. J. Surg. 61, 971-978 Cranky J J, Canos A J, Sull W J & Grass A M (1975) Surg. Cynecol. Obstet. 141, 331-339 Cranley J J, Canos A J & Sull W J (1976) Arch. Surg. I l l , 34-36 DeWeesc J A & Rogoff S M (1959) Am. J. Roentgenol. 81, 841-854 DeWeese J A & Rogoff S M (1963) Surgery. 53, 99-107 Duffy G J, D'Auria D, Brien T G, Ormond D & Mehigan J A (1973) Br. Med. J. 1, 712-714 Evans D S (1970) Br. J. Surg. 57. 726-728 Evans D S & Cockett F B (1969) Br. Med. J. 2, 802-804 Flane C, Kakkar V V & Clarke M B (1968) Br. J. Surg. 55, 742-747 Hull R, Aken W G van, Hirsh J, Gallus A S, Hoicka G, Turpie A G G, Walker I & Gent M (1976) Circulation, 53, 696-700 Hume M, Turner R H, Kuriakose T X & Surprenant J (1976) / . Bone Jt. Surg. 58-A, 933-939 Lambie J M, Mahaffy R G, Barber D C, Karmody A M, Scott M M & Matheson N A (1970) Br. Med. J. 2,142-143 McUroy R F (1972) Br. J. Surg. 59, 133-135 McLachlin J, Richards T & Paterson J C (1962) Arch. Surg. 85,

Meadway J, Nicolaides A N, Walker C J & O'Connell J D (1975) Br. Med. J. 4, 552-554 Morris G K & Mitchell J R A (1977) Br. Med. J. 1, 264-266 Negus D, Pinto D J, Le Quesne L P, Brown N & Chapman M (1968) Br. J. Surg. 55, 835-839 Provan J L (1965) Br. Med. J. 2, 334-337 Roberts V C (1975) Br. Med. J. 3, 455-458 Rosenthall L & Greyson N D (1970) Radiology, 94,413-416 Sevitt S & Gallagher N (1961) Br. J. Surg. 48, 475^189 Sigel B, Popky G L, Wagner D K, Boland J P, Mapp E M & Feigl P (1968) Surg. Gynecol. Obstet. 127, 339-350 Strandness D E Jr, Schultz R D, Sumner D S & Rushmer R F (1967) Am. J. Surg. 113, 311-320 Thomas M L (1970) Br. J. Radiol. 43, 528-530 Thomas M L (1972) Arch. Surg. 104,145-151 Thomas M L, Andress M R, Browse N L, Fletcher EWL, Phillips J D, Pim H P, McAllister V, Stephenson R H & Tonge K (1970) Am. J. Roentgenol. 110, 725-733 Thomas M L, McAllister V & Tonge K (1971) Clin. Radiol. 22, 495-501 Webber M M, Webb R C & Cragin M D (1969) In: Medical radioisotope scintigraphy, vol. n , pp. 773-780 (Proceedings of a symposium held in Salzburg, 6-15 August 1968). International Atomic Energy Agency, Vienna Webber M M, Pollak E W, Victery W, Cragin M, Resnick L H & Grollman J H Jr (1974) Radiology, 111, 645-650 Wheeler H B, Mullick S C, Anderson J N & Pearson D (1971) Surgery, 70, 20-28 Yao S T, Gourmos C & Hobbs J T (1972) Lancet, 1, \-A

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Diagnosis of deep-vein thrombosis.

British Medical Bulletin (1978) Vol. 34, No. 2, pp. 163-167 DIAGNOSIS OF DEEP-VEIN THROMBOSIS N Browse thennography, thefibrinogenuptake test, x-ray...
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